期刊
JOURNAL OF NEUROSCIENCE
卷 31, 期 4, 页码 1292-1301出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4611-10.2011
关键词
-
资金
- Canadian Lung Association
- Quebec Health Research Funds (FRSQ)
- Canadian Thoracic Society
- Canadian Institutes of Health Research
- Ontario Thoracic Society-Canadian Lung Association
The analgesic properties of the opium poppy Papever somniferum were first mentioned by Hippocrates around 400 BC, and opioid analgesics remain the mainstay of pain management today. These drugs can cause the serious side-effect of respiratory depression that can be lethal with overdose, however the critical brain sites and neurochemical identity of the neurons mediating this depression are unknown. By locally manipulating neurotransmission in the adult rat, we identify the critical site of the medulla, the preBotzinger complex, that mediates opioid-induced respiratory depression in vivo. Here we show that opioids at the preBotzinger complex cause respiratory depression or fatal apnea, with anesthesia and deep-sleep being particularly vulnerable states for opioid-induced respiratory depression. Importantly, we establish that the preBotzinger complex is fully responsible for respiratory rate suppression following systemic administration of opioid analgesics. The site in the medulla most sensitive to opioids corresponds to a region expressing neurokinin-1 receptors, and we show in rhythmically active brainstem section in vitro that neurokinin-1 receptor-expressing preBotzinger complex neurons are selectively inhibited by opioids. In summary, neurokinin-1 receptor-expressing preBotzinger complex neurons constitute the critical site mediating opioid-induced respiratory rate depression, and the key therapeutic target for its prevention or reversal.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据